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Controlling protein function by fine-tuning conformational flexibility
In a living cell, protein function is regulated in several ways, including post-translational modifications (PTMs), protein-protein interaction, or by the global environment (e.g. crowding or phase separation). While site-specific PTMs act very locally on the protein, specific protein interactions t...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375816/ https://www.ncbi.nlm.nih.gov/pubmed/32697684 http://dx.doi.org/10.7554/eLife.57180 |
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author | Schmid, Sonja Hugel, Thorsten |
author_facet | Schmid, Sonja Hugel, Thorsten |
author_sort | Schmid, Sonja |
collection | PubMed |
description | In a living cell, protein function is regulated in several ways, including post-translational modifications (PTMs), protein-protein interaction, or by the global environment (e.g. crowding or phase separation). While site-specific PTMs act very locally on the protein, specific protein interactions typically affect larger (sub-)domains, and global changes affect the whole protein non-specifically. Herein, we directly observe protein regulation under three different degrees of localization, and present the effects on the Hsp90 chaperone system at the levels of conformational steady states, kinetics and protein function. Interestingly using single-molecule FRET, we find that similar functional and conformational steady states are caused by completely different underlying kinetics. We disentangle specific and non-specific effects that control Hsp90’s ATPase function, which has remained a puzzle up to now. Lastly, we introduce a new mechanistic concept: functional stimulation through conformational confinement. Our results demonstrate how cellular protein regulation works by fine-tuning the conformational state space of proteins. |
format | Online Article Text |
id | pubmed-7375816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-73758162020-07-24 Controlling protein function by fine-tuning conformational flexibility Schmid, Sonja Hugel, Thorsten eLife Biochemistry and Chemical Biology In a living cell, protein function is regulated in several ways, including post-translational modifications (PTMs), protein-protein interaction, or by the global environment (e.g. crowding or phase separation). While site-specific PTMs act very locally on the protein, specific protein interactions typically affect larger (sub-)domains, and global changes affect the whole protein non-specifically. Herein, we directly observe protein regulation under three different degrees of localization, and present the effects on the Hsp90 chaperone system at the levels of conformational steady states, kinetics and protein function. Interestingly using single-molecule FRET, we find that similar functional and conformational steady states are caused by completely different underlying kinetics. We disentangle specific and non-specific effects that control Hsp90’s ATPase function, which has remained a puzzle up to now. Lastly, we introduce a new mechanistic concept: functional stimulation through conformational confinement. Our results demonstrate how cellular protein regulation works by fine-tuning the conformational state space of proteins. eLife Sciences Publications, Ltd 2020-07-22 /pmc/articles/PMC7375816/ /pubmed/32697684 http://dx.doi.org/10.7554/eLife.57180 Text en © 2020, Schmid and Hugel http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Schmid, Sonja Hugel, Thorsten Controlling protein function by fine-tuning conformational flexibility |
title | Controlling protein function by fine-tuning conformational flexibility |
title_full | Controlling protein function by fine-tuning conformational flexibility |
title_fullStr | Controlling protein function by fine-tuning conformational flexibility |
title_full_unstemmed | Controlling protein function by fine-tuning conformational flexibility |
title_short | Controlling protein function by fine-tuning conformational flexibility |
title_sort | controlling protein function by fine-tuning conformational flexibility |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375816/ https://www.ncbi.nlm.nih.gov/pubmed/32697684 http://dx.doi.org/10.7554/eLife.57180 |
work_keys_str_mv | AT schmidsonja controllingproteinfunctionbyfinetuningconformationalflexibility AT hugelthorsten controllingproteinfunctionbyfinetuningconformationalflexibility |